1-Bromo-2,2-difluorocyclopropane

ABSTRACT

New compounds 1-chloro-1,2,2-trifluorocyclopropane and 1-bromo2,2-difluorocyclopropane have been found useful as general inhalation anesthetics.

United States Patent n91 ONeill et al.

[ 51 Sept. 2, 1975 l-BROMO-2,2-DIFLUORQCYCLOPROPANE [75] Inventors: Gerald J. O'Neill, Arlington;

Charles A. Billings, Concord; Charles W. Simons, Bedford all of Mass.

[62] Division of Ser. No. 258,957. June 2. 1972. Pm. No.

[52] US. Cl. 260/648 F; 160/648 F [5 1} Int. Cl. C07c 23/04 [58] Field of Search 260/648 F [56] References Cited UNITED STATES PATENTS 3.349.136 10/[967 Boudakian ct al. 260/648 F Primary Emminer-D. Horwitz Attorney. Agent. or Firm-Armand McMillan; C. E. Parker [57] ABSTRACT New compounds I -chl0ro-l 2,2-trifluorocyclopropane and l-br0m0-2.Z-difluorocyclopropane have been found useful as general inhalation anesthetics.

1 Claim, N0 Drawings This is a division of application Ser. No. 258.957. filed June 2. l972 now U.S. Pat. No. 3.825.606.

Although a certain number of halogenated hydrocarbon compounds have joined the ranks of useful anesthetics in the recent past. little has been added to the understanding of the mode of action of chemical compounds in this physiological role. and the relationships of the differences between fairly closely similar compounds with either their toxic or therapeutic properties remain substantially unidentified. In view of this situation. the discovery of additional substances possessing a desirable combination of properties for anesthetic purposes still lies beyond the scope of routine expertise.

SUMMARY OF THE INVENTION It has now been discovered that newly synthesized 1-ehlorol .2.2-trifluorocyclopropane and l-bromo- 2.2-difluorocyclopropane possess high potency as general anesthetics when administered to inhalationanesthetic-susceptible organisms.

DETAILED DESCRIPTION It should be noted that this method of synthesis does not always yield the compound desired possibly because. in some instances, either the cyclization does not take place or, if it does. the resulting cyelocompound is unstable at carbcne generating temperatures.

EXAMPLE 1 To prepare the chlorocyclopropane compound of the present invention. 4-t-butylpyrocatechol. 1 part by weight. is placed in a stainless steel autoclavev The autoclave is sealed, evacuated. and cooled to 78C. l-Chlorol-fluoroethylene. 80.5 parts. and hexafluoropropylene oxide. 40.3 parts. are then introduced into the apparatus. The system is heated for 8 hours at 185C. After cooling to room temperature. the con tents of the autoclave are transferred to a -l 96C trap.

Materials boiling below room temperature are allowed to escape and the residue is purified by operative vapor chromatography. The produce has a molecular weight of 130. a boiling point of 3 lC and a d of L358 g/ml.

EXAMPLE 2 To obtain the bromocyclobutane compound. 4-tbutylpyrocatechol. 1 part by weight. is placed in a stainless steel autoclave. The autoclave is sealed. evacuated. and cooled to 78C. l-Vinyl bromide. 116.2 parts. and hexafluoropropylene oxide. 46.4 parts. are then introduced into the apparatus. The system is heated for 8 hours at I85C. After cooling to room temperature. the contents of the autoclave are transferred to a -196C trap. Materials boiling below room temperature are allowed to escape and the residue is purified by preparative vapor chromatography. The product has a molecular weight of 157. a boiling point of 68 to 685C and a dfi of 1.725 g/ml.

EXAMPLE 3 The physiological effects of the two fluorocyclopropanes were demonstrated as follows. using a standard test for evaluation of inhalation anesthetics similar to that described by Robbins [.l. Pharmacology and Experimental Therapeutics 86. 197 l946l].

Mice were exposed to the anesthetic for a period of [0 minutes in a rotating drum. Observations were then made of the pinch reflex. the corneal reflex and the return of the righting reflex. At least four graded doses were employed to determine the minimum concentration required to anesthetize 50% of the mice used (AC-,0) and the minimum concentration required to kill 50% of the mice (LG-, The anesthetic index (Al) was then calculated from these minimum concentrations. The results of these tests are summarized in the following table.

ANESTHETIC PROPERTIES *When two figures are given. the actual \alue of the anesthetic index lies between these two figures.

For comparison. keeping in mind that other differences in properties also exist. the fact may be considered that the widely used l.l.l-trifluoro2-bromo-2- chloroethane showed an AI of 3.2 when tested under the same conditions.

What is claimed is:

l. l-Bromo-Z.Z-difluorocyclopropane. 

1. 1-BROMO- 2,2-DIFLUOROCYCLOPROPANE. 